Dataset Information

Proteomic analysis identifies novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy

ABSTRACT: Resistance to Human Epidermal Growth Factor Receptor (HER)-targeted cancer therapies appear to be occurring via common pathways, despite differences in their mechanism of action. This suggests that combination therapies targeting alternative pathways will be needed to overcome resistance. We have used a global proteomics approach to identify common signaling nodes that are required for driving HER2-independent resistance mechanisms to the pan-HER family kinase inhibitors AZD8931 and lapatinib. A novel set of epithelial–to-mesenchymal transition (EMT) associated proteins linked to resistance to pan-HER family targeted therapy was identified. We demonstrate that a sub-set of these genes are predictive of prognosis within the ERBB2 subtype of breast cancers and are worthy of further study in the context of preventing resistance to anti-HER family agents. Furthermore, targeting these pathways, perhaps via combination with galectin-1 or Axl inhibitors may provide additional strategies for the treatment of resistant tumours.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Thierry Le Bihan

LAB HEAD: Thierry Le Bihan

PROVIDER: PXD002057 | Pride | 2016-02-22

REPOSITORIES: Pride

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Publications

Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy.

Creedon Helen H Gómez-Cuadrado Laura L Tarnauskaitė Žygimantė Ž Balla Jozef J Canel Marta M MacLeod Kenneth G KG Serrels Bryan B Fraser Craig C Unciti-Broceta Asier A Tracey Natasha N Le Bihan Thierry T Klinowska Teresa T Sims Andrew H AH Byron Adam A Brunton Valerie G VG

Oncotarget 20160301 10

Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies in the treatment of HER2-positive breast cancer is a major clinical problem. To identify pathways linked to resistance, we generated HER2-positive breast cancer cell lines which are resistant to either lapatinib or AZD8931, two pan-HER family kinase inhibitors. Resistance was HER2 independent and was associated with epithelial-to-mesenchymal transition (EMT), resulting in increased proliferation and migration of the ...[more]

PMID: 26883193

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Dataset Information

Proteomic analysis identifies novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy

Publications

Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy.

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